Merck Sharp & Dohme Corp. v. Albrecht

• Decision Date: 20 May 2019
• Docket Number: No. 17-290,17-290
• Parties: MERCK SHARP & DOHME CORP., Petitioner v. Doris ALBRECHT, et al.
• Court: U.S. Supreme Court

139 S.Ct. 1668

MERCK SHARP & DOHME CORP., Petitioner

v.Doris ALBRECHT, et al.

No. 17-290

Supreme Court of the United States.

Argued January 7, 2019

Decided May 20, 2019

Shay Dvoretzky, Washington, DC, for petitioner.

Malcolm L. Stewart, for the United States as amicus curiae, by special leave of the Court, supporting the petitioner.

David C. Frederick, Washington, DC, for respondents.

Stephanie Parker, Jones Day, Atlanta, GA, Benjamin M. Flowers, Jones Day, Columbus, OH, Shay Dvoretzky, Yaakov M. Roth, Jeffrey R. Johnson, Jones Day, Washington, DC, for petitioner.

David C. Frederick, Brendan J. Crimmins, Jeremy S.B. Newman, Kellogg, Hansen, Todd, Figel & Frederick, P.L.L.C., Washington, DC, for respondents.

Justice BREYER delivered the opinion of the Court.

When Congress enacted the Federal Food, Drug, and Cosmetic Act, ch. 675, 52 Stat. 1040, as amended, 21 U.S.C. § 301 et seq. , it charged the Food and Drug Administration with ensuring that prescription drugs are "safe for use under the conditions prescribed, recommended, or suggested" in the drug’s "labeling." § 355(d). When the FDA exercises this authority, it makes careful judgments about what warnings should appear on a drug’s label for the safety of consumers.

For that reason, we have previously held that "clear evidence" that the FDA would not have approved a change to the drug’s label pre-empts a claim, grounded in state law, that a drug manufacturer failed to warn consumers of the change-related risks associated with using the drug. See Wyeth v. Levine , 555 U. S. 555, 571, 129 S.Ct. 1187, 173 L.Ed.2d 51 (2009). We here determine that this question of pre-emption is one for a judge to decide, not a jury. We also hold that "clear evidence" is evidence that shows the court that the drug manufacturer fully informed the FDA of the justifications for the warning required by state law and that the FDA, in turn, informed the drug manufacturer that the FDA would not approve a change to the drug’s label to include that warning.

I

The central issue in this case concerns federal pre-emption, which as relevant here, takes place when it is " ‘impossible for a private party to comply with both state and federal requirements.’ " Mutual Pharmaceutical Co. v. Bartlett , 570 U. S. 472, 480, 133 S.Ct. 2466, 186 L.Ed.2d 607 (2013). See also U. S. Const., Art. VI, cl. 2. The state law that we consider is state common law or state statutes that require drug manufacturers to warn drug consumers of the risks associated with drugs. The federal law that we consider is the statutory and regulatory scheme through which the FDA regulates the information that appears on brand-name prescription drug labels. The alleged conflict between state and federal law in this case has to do with a drug that was manufactured by petitioner Merck Sharp & Dohme and was administered to respondents without a warning of certain associated risks.

A

The FDA regulates the safety information that appears on the labels of prescription drugs that are marketed in the United States. 21 U.S.C. § 355(b)(1)(F) ; 21 C.F.R. § 201.57(a) (2018). Although we commonly understand a drug’s "label" to refer to the sticker affixed to a prescription bottle, in this context the term refers more broadly to the written material that is sent to the physician who prescribes the drug and the written material that comes with the prescription bottle when the drug is handed to the patient at the pharmacy. 21 U.S.C. § 321(m). These (often lengthy) package inserts contain detailed information about the drug’s medical uses and health risks. § 355(b)(1)(F) ; 21 C.F.R. § 201.57(a).

FDA regulations set out requirements for the content, the format, and the order of the safety information on the drug label. § 201.57(c). Those regulations require drug labels to include, among other things: (1) prominent "boxed" warnings about risks that may lead to death or serious injury; (2) contraindications describing any situation in which the drug should not be used because the risk of use outweighs any therapeutic benefit; (3) warnings and precautions about other potential safety hazards; and (4) any adverse reactions for which there is some basis to believe a causal relationship exists between the drug and the occurrence of the adverse event. Ibid.

As those requirements make clear, the category in which a particular risk appears on a drug label is an indicator of the likelihood and severity of the risk. The hierarchy of label information is designed to "prevent overwarning" so that less important information does not "overshadow" more important information. 73 Fed. Reg. 49605–49606 (2008). It is also designed to exclude "[e]xaggeration of risk, or inclusion of speculative or hypothetical risks," that "could discourage appropriate use of a beneficial drug." Id ., at 2851.

Prospective drug manufacturers work with the FDA to develop an appropriate label when they apply for FDA approval of a new drug. 21 U.S.C. §§ 355(a), 355(b), 355(d)(7) ; 21 C.F.R. § 314.125(b)(6). But FDA regulations also acknowledge that information about drug safety may change over time, and that new information may require changes to the drug label. §§ 314.80(c), 314.81(b)(2)(i). Drug manufacturers generally seek advance permission from the FDA to make substantive changes to their drug labels. However, an FDA regulation called the "changes being effected" or "CBE" regulation permits drug manufacturers to change a label without prior FDA approval if the change is designed to "add or strengthen a ... warning" where there is "newly acquired information" about the "evidence of a causal association" between the drug and a risk of harm. 21 C.F.R. § 314.70(c)(6)(iii)(A).

B

Petitioner Merck Sharp & Dohme manufactures Fosamax, a drug that treats and prevents osteoporosis in postmenopausal women. App. 192; In re Fosamax (Alendronate Sodium) Products Liability Litigation , 852 F. 3d 268, 271, 274–275 (CA3 2017). Fosamax belongs to a class of drugs called "bisphosphonates." Fosamax and other bisphosphonates work by affecting the "bone remodeling process," that is, the process through which bones are continuously broken down and built back up again. App. 102, 111. For some postmenopausal women, the two parts of the bone remodeling process fall out of sync; the body removes old bone cells faster than it can replace them. That imbalance can lead to osteoporosis, a disease that is characterized by low bone mass and an increased risk of bone fractures. Fosamax (like other bisphosphonates) slows the breakdown of old bone cells and thereby helps postmenopausal women avoid osteoporotic fractures. Id., at 102.

However, the mechanism through which Fosamax decreases the risk of osteoporotic fractures may increase the risk of a different type of fracture. Id ., at 400–444, 661–663. That is because all bones—healthy and osteoporotic alike—sometimes develop microscopic cracks that are not due to any trauma, but are instead caused by the mechanical stress of everyday activity. Id., at 102. Those so-called "stress fractures" ordinarily heal on their own through the bone remodeling process. But, by slowing the breakdown of old bone cells, Fosamax and other bisphosphonates may cause stress fractures to progress to complete breaks that cause great pain and require surgical intervention to repair.Id., at 106–109, 139, 144–145. When that rare type of complete, low-energy fracture affects the thigh bone, it is called an "atypical femoral fracture." Id., at 101.

The Fosamax label that the FDA approved in 1995 did not warn of the risk of atypical femoral fractures. 852 F. 3d at 274–275. At that time, Merck’s scientists were aware of at least a theoretical risk of those fractures. Indeed, as far back as 1990 and 1991, when Fosamax was undergoing preapproval clinical trials, Merck scientists expressed concern in internal discussions that Fosamax could inhibit bone remodeling to such a " ‘profound’ " degree that "inadequate repair may take place" and " ‘micro-fractures would not heal.’ " App. 111–113. When Merck applied to the FDA for approval of Fosamax, Merck brought those theoretical considerations to the FDA’s attention. 852 F. 3d at 274–275. But, perhaps because the concerns were only theoretical, the FDA approved Fosamax’s label without requiring any mention of this risk. Ibid.

Evidence connecting Fosamax to atypical femoral fractures developed after 1995. Merck began receiving adverse event reports from the medical community indicating that long-term Fosamax users were suffering atypical femoral fractures. App. 122–125. For example, Merck received a report from a doctor who said that hospital staff had begun calling atypical femoral fractures the " ‘Fosamax Fracture’ " because " ‘100% of patients in his practice who have experienced femoral fractures (without being hit by a taxicab), were taking Fosamax... for over 5 years. ’ " Id., at 126. Merck performed a statistical analysis of Fosamax adverse event reports, concluding that these reports revealed a statistically significant incidence of femur fractures. 3 App. in No. 14–1900 (CA3), pp. A1272–A1273, A1443. And about the same time, Merck began to see numerous scholarly articles and case studies documenting possible connections between long-term Fosamax use and atypical femoral fractures. App. 106–110, 116–122.

In 2008, Merck applied to the FDA for preapproval to change Fosamax’s label to add language to both the "Adverse Reaction[s]" and the "Precaution[s]" sections of the label. Id., at 670. In particular, Merck proposed adding a reference to " ‘low-energy femoral shaft fracture ’ " in the Adverse Reactions section, and cross-referencing a longer discussion in the Precautions section that focused on the risk of stress fractures associated with Fosamax. Id., at 728. The FDA approved the addition to the Adverse Reactions section, but rejected Merck’s proposal to warn of a risk of "stress fractures." Id., at 511–512. The FDA explained that Merck’s "justification" for the...